The aim of the proposed research continue to include 1) the establishment of further primary (specific) chromosome changes in bladder cancer akin to those already described by us and others (e.g., 5q-/-5, +7, 9q-/-9, 11p-/illq), 2) correlation of the cytogenetic findings with a number of parameters of each case (histology, including stage and grade, marker status, course of disease) to possibly delineate subtypes of bladder cancer on the basis of the primary karyotypic change, 3) to develop the application of in-situ hybridization techniques utilizing repeat sequenced probes for the recognition of at least some of the karyotypic changes (e.g., +7, -9) in interphase nuclei of superficial bladder lesions (e.g., carcinoma-in-situ) which often cannot be examined cytogenetically and 4) molecular studies of bladder cancer, as related to the chromosome changes, e.g., gene modification or altered gene expression. To further delineate primary chromosome changes much emphasis will be put on obtaining bladder cancers with a single cytogenetic anomaly or event. Since correlations appear to exist between the primary karyotypic event and prognosis (e.g., relatively good prognosis for tumors with +7 or -9 and poor prognosis for those with 5q-, i5p, or 11p-), such studies will be extended not only to larger series of tumors with known primary chromosome changes, but also to newly established subtypes. The molecular studies will be especially important in characterizing superficial bladder lesions in which cytogenetic analyses are usually not successful and in which current predictive parameters of recurrence or invasiveness are not reliable. Particularly promising appears to be in situ hybridization techniques with appropriate probes of interphase nuclei of superficial or small lesions to demonstrate such cytogenetic changes as -7 and +9 (relatively good prognosis) or loss of the Y (poor prognosis).